For over a half decade, we have questioned whether OCT can measure macrophages. It appears in several reviews and in the cardiovascular chapter of the textbook I wrote. There are two reasons, one based on the analysis of papers on the topic and one looking at the data base of coronary arteries we used for polarization assessment in coronary arteries.

1."The second marker is the ability of OCT to identify plaque macrophages (125-126). This is an intriguing concept put forward by a group at MGH and is an important marker to be evaluated in future studies. However, there is only one study that attempts to quantify this and because of several concerns discussed below, confirmation of these results seems appropriate. First, the authors neither used a ‘training set’ nor predetermined criteria for what constituted a positive or negative predictive value in the OCT image, but determined the criteria after examining the measured data set (125). They established the value for raw OCT data to be between 6.15% and 6.35%, giving 100% sensitivity and specificity. A different statistical approach may be useful to examine. It is of note that they did not appear to use these values for interpreting their subsequent in vivo study, which did not have histological validation (126). Second, they performed a median filter over a 3 X 3 square kernel that corresponds to an effective axial resolution for macrophages worse than 30 µm. Therefore, the macrophages would either need to be densely packed or greater than 30 µm in diameter. Third, they used the mean background noise for their calculation. The problem with this is best illustrated with a simulation, where we take the case of two different background variations. In the first case, the background has low pixel variations, between 1 and 3. In the second case, the pixels vary from 1 to 9. If we make the concentration of macrophages on both images the same and that macrophages have a constant value of 50, the normalized standard deviation (NSD) on the first image will be 50.31%, and on the second 46.77%, meaning that the concentration of macrophages on image 1 is higher than on image 2 and this is not true. Finally, when the same group applied the approach in vivo, there was minimal difference between the culprit plaque and remote regions (5.54±1.48 vs 5.38±1.56) and in culprit lesions in unstable vs stable plaque (5.91±2.06 vs 4.21±1.74) (126). Particularly when no training set has been established with histologic correlations and the concern over variation due to background noise, it is unclear how these small variations will be diagnostic when spread over a large population. Furthermore, as discussed above, it is unclear whether macrophage concentrations increase in the high-risk plaque before or after rupture. While the work on OCT assessments of macrophages remains intriguing, future work in this area is needed to confirm the results and determine ultimate clinical value"